Description:
The purpose of this study is to evaluate the safety and the feasibility, and the success of
engraftment of the introduction of Cal-1 gene-transduced haematopoietic cell populations (Ttn
and HSPCtn) in patients with HIV-1-related high-risk lymphoma.
Title
- Brief Title: A Study Evaluating the Safety of Cal-1 (LVsh5/C46) Drug Product in HIV-1 Infected Patient With High Risk Lymphoma
- Official Title: A Phase I/II Study of the Safety of CD34+ Haematopoietic Stem/Progenitor Cells and CD4+ T Lymphocytes Transduced With LVsh5/C46, a Dual Anti-HIV Gene Transfer Construct, in HIV-1 Infected Patients With High-risk Lymphoma
Clinical Trial IDs
- ORG STUDY ID:
P 141004
- SECONDARY ID:
2015-004453-41
- NCT ID:
NCT03593187
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Cal-1 (LVsh5/C46) drug product | | Cal-1( LVsh5/C46) drug product |
Purpose
The purpose of this study is to evaluate the safety and the feasibility, and the success of
engraftment of the introduction of Cal-1 gene-transduced haematopoietic cell populations (Ttn
and HSPCtn) in patients with HIV-1-related high-risk lymphoma.
Detailed Description
Trial Arms
Name | Type | Description | Interventions |
---|
Cal-1( LVsh5/C46) drug product | Experimental | | - Cal-1 (LVsh5/C46) drug product
|
Eligibility Criteria
Inclusion Criteria:
Eligible subjects will undergo screening assessments at three time points:
- Screening 1 at the beginning of chemotherapy,
- Screening 2 (first "check-point") after the harvest for CD34,
- Screening 3 (second "check-point") before the ASCT procedure. Potential subjects must
satisfy all of the inclusion criteria to be enrolled in the study and proceed with the
first apheresis (day -39).
In-A. Prior to any study-related procedures, signed informed consent indicating that they
understand the purpose, risks and procedures required for the study and are willing to
participate in the study In-B. Individuals aged 18 to 60 years of age (inclusive) at time
of consent In-C. Women with child-bearing potential must be on adequate effective
contraception (continuous progestative contraception) In-D. Documented HIV-1 infection at
or before the time of lymphoma diagnosis In-E. Treatment with antiretroviral agents
(excluding NNRTI) introduced or optimized at the time of screening
In-F. Biopsy-proven lymphoma meeting one of the following criteria:
1. 1. Intermediate- or high-grade B-cell non-Hodgkin lymphoma, meeting 1 of the following
criteria:
- in first complete remission with high-risk features such as T-cell lymphoma and
plasmablastic lymphoma (after multidisciplinary consultation regarding the
indication of ASCT in this context). The decision of ASCT is independent of the
present clinical trial.
- in partial remission
- relapsed after initial complete remission
- failed induction therapy but responds to salvage therapy (i.e., chemosensitive
disease)
2. Hodgkin lymphoma, meeting 1 of the following criteria:
- in first or greater relapse after initial complete remission
- in partial remission
- failed induction therapy but responds to salvage therapy (i.e. chemosensitive
disease)
3. High-risk lymphoma requiring a treatment with combined chemotherapy and autologous
stem cell transplantation (ASCT)
Exclusion Criteria:
Ex-A. -Left ventricular ejection fraction <50% at Screening 1:
Ex-B. Abnormal biochemistry at Screening 1:
Alanine and/or aspartate aminotransferase (ALT/AST) >10 x upper limit of normal (ULN) Total
bilirubin > 2.5 x ULN Creatinine clearance <60ml/min Ex-C. Severe coagulopathy Ex-D.
Prothombin time > 2x ULN Ex-E. Evidence of co-infection with hepatitis B virus (HBsAg+),
hepatitis C virus, West Nile Virus, or Human T-lymphotropic virus (HTLV-1) as detected at
Screening 1 Ex-F. Stay in West Nile Virus endemic area less than 6 weeks prior to CD34+
collection Ex-G. Evidence of non-treated opportunistic infection during the pre-infusion
period Ex-H. Evidence of not-treated CNS involvement of lymphoma at Screening 1 Ex-I.
Isolated CNS relapse of the lymphoma without other evidence of active disease at Screening
1 Ex-J. Known hypersensitivity to G-CSF (Neupogen™) or plerixafor (Mozobil™) Ex-K. Evidence
of uncontrolled HIV-1 viremia at screening 2 and/or 3 (plasma HIV-1 RNA ≥ 1.000 copies/ml
confirmed in 2 successive blood samples) Ex-L. Evidence of chemoresistant lymphoma at
screening 2 Ex-M. Any contra-indication to ASCT at any time during the pre-infusion period
Ex-N. Participation in any study involving any investigational drug or medical device
within 3 months prior to Screening 1 Ex-O. Receipt of a vaccine for HIV-1 or any gene
transfer product at any time Ex-P. Subjects who will not accept transfusions of blood
products Ex-Q. Pregnant or breast-feeding woman at any time Ex-R. Woman of child-bearing
potential not under adequate contraceptive protection at any time Ex-S. Inability to
understand and provide informed consent Psychological or psychiatric disability thought to
be clinically significant in the opinion of the investigator
Maximum Eligible Age: | 60 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Incidence of adverse event post transplant |
Time Frame: | 24 months post-transplant |
Safety Issue: | |
Description: | to evaluate the procedure safety |
Secondary Outcome Measures
Measure: | Overall survival |
Time Frame: | 24 months post-transplant |
Safety Issue: | |
Description: | |
Measure: | Absence of detection of vector-derived Replication competent lentivirus (RCL) |
Time Frame: | 24 months post-transplant |
Safety Issue: | |
Description: | |
Measure: | Frequency and severity of clinical adverse events |
Time Frame: | 24 months post-transplant |
Safety Issue: | |
Description: | as assessed by the United States national Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) |
Measure: | Absence of tropism shift from R5 to dual/mixed or X4 at any point after Day 0 |
Time Frame: | 24 months post-transplant |
Safety Issue: | |
Description: | |
Measure: | Quantify gene transfer efficiency and expression |
Time Frame: | 24 months post-transplant |
Safety Issue: | |
Description: | extent of HSPCtn and Ttn survival as measured by Cal-1 marking and expression in peripheral blood |
Measure: | Time to restart antiretroviral therapy |
Time Frame: | 24 months post-transplant |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Assistance Publique - Hôpitaux de Paris |
Trial Keywords
- HIV-1
- Lymphoma
- Gene therapy
Last Updated
April 14, 2021